Authors:
Nonhlanhla N. Mkhize, Bo Zhang, Caroline Brackett, Peter James Elyanu, Asa Tapley, Sufia Dadabhai, Jiani Hu, Bich T. N. Do, Daniel J. Schuster, Jack Heptinstall, Sheetal Sawant, Kelly Seaton, Marcella Sarzotti-Kelsoe, Aaron Hudson, Yutong Jin, Sinethemba Bhebhe, Haajira Kaldine, Prudence Kgagudi, Tandile Modise, Nyaradzo M. Mgodi, Jessica Andriesen, April K. Randhawa, Leigh H. Fisher, Jia Jin Kee, Craig A. Magaret, James Peng, Avi Kenny, Lindsay N. Carpp, Zhe Chen, Siyu Heng, Manuel Villaran, Azwidihwi Takalani, Bert Le Roux, Eduan Wilkinson, Jackline Odhiambo, Parth Shah, Laura Polakowski, Margaret Yacovone, Taraz Samandari, Zvavahera Chirenje, Joseph Makhema, Ethel Kamuti, Katanekwa Njekwa, Harriet Nuwagaba-Biribonwoha, Allan Baguma, Sharlaa Badal-Faesen, William Brumskine, Soritha Coetzer, Rodney Dawson, Sinead Delany-Moretlwe, Andreas Henri Diacon, Samantha Fry, Katherine Gill, Anda Madikida, Zaheer Ahmed Ebrahim Hoosain, Mina C. Hosseinipour, Mubiana Inambao, Craig Innes, Steve Innes, Dishiki Kalonji, Humphrey Mwape, Priya Kassim, Melvin C. Kamanga, William Kilembe, Fatima Laher, Mookho Malahleha, Vongane Louisa Maluleke, Grace Mboya, Philister Adhiambo Madiega, Kirsten McHarry, Essack Mitha, Yajna Duki, Pamela Mda, Moroesi Moerane, Tumelo Moloantoa, Simpson Nuwamanya, Sharana Mahomed, Vimla Naicker, Anusha Nana, Annet Nanvubya, Barbarah Kawoozo, Maphoshane Nchabeleng, Walter Otieno, Elsje Louise Potgieter, Disebo Potloane, Zelda Punt, Jamil Said, Yashna Singh, Sheetal Kassim, Dorothie van der Vendt, Mohammed Siddique Tayob, Yacoob Vahed, Deo Ogema Wabwire, James G. Kublin, Linda-Gail Bekker, Lawrence Corey, Glenda E. Gray, Yunda Huang, Philip Kotze, Nigel Garrett, John Hural, Guido Ferrari, Erica Andersen-Nissen, David Montefiori, Penny L. Moore, M. Juliana McElrath, Georgia D. Tomaras, Peter B. Gilbert & CoVPN 3008 Study Team
Abstract:
People with HIV (PWH) are understudied in COVID-19 vaccine trials, leaving knowledge gaps on whether the identified immune correlates of protection also hold in PWH. CoVPN 3008 (NCT05168813) enrolled predominantly PWH and reported lower COVID-19 incidence for a Hybrid vs. Vaccine Group (baseline SARS-CoV-2-positive and one mRNA-1273 dose vs. negative and two doses). Using case-cohort sampling, antibody markers at enrolment (M0) and four weeks post-final vaccination (Peak) are assessed as immune correlates of COVID-19. For the Hybrid Group [n = 287 (195 PWH)], all M0 markers inversely correlate with COVID-19 through 230 days post-Peak, with 50% inhibitory dilution BA.4/5 neutralizing antibody titer (nAb-ID50 BA.4/5) the strongest and only independent correlate (HR per 10-fold increase=0.46, 95% CI 0.28, 0.75; P = 0.002). For the Vaccine Group [n = 115 (86 PWH)], Peak nAb-ID50 BA.4/5 correlates with reduced COVID-19 risk (1.9%, 1.1%, and 0.3% at titers 10, 100, and 1000 AU/ml) through 92, but not 165, days post-Peak. Using multivariable Cox analysis of binding and nAb, nAb titers predict COVID-19 in PWH. Two doses of a 100-µg Ancestral strain mRNA vaccine in baseline-SARS-CoV-2-negative individuals elicit sufficient cross-reacting Omicron antibodies to reduce COVID-19 incidence for 90 days post-Peak, but viral evolution and waning antibodies abrogate this protection thereafter.
